As the receptor relating to analgesic action on central nerve, opioid receptors have been revealed, and the opioid receptors are classified into three types .mu., .delta. and .kappa.. .beta.-endorphin which is one of the endogeneous opioid peptides showing strong analgesic action, has been considered as a non-selective agonist having affinities to both .mu. and .delta. receptors. However, detailed study using antagonists each of which is selective to each type of the opioid receptors has revealed that .beta.-endorphin has an additional site on which it acts, in addition to the known three types of receptors. As the action site, .epsilon.-type receptor is drawing attention recently.
Morphine having morphinan skeleton is known as a strong analgesic for a long time, and is widely used now. However, this drug has serious side effects which are clinically problematic, such as addiction, respiratory depression and smooth muscle-depressomotor action (constipation), and it has been clarified that these side effects are exhibited through .mu. receptors. Since use of the drug requires strict control, a strong analgesic acting on the central nerve, which may be safely used, is desired.
On the other hand, the above-mentioned .beta.-endorphin has been reported not to show cross tolerance to morphine which is .mu.-agonist. Agonists at .epsilon.-receptor are expected as analgesics free from the side effects which the .mu.-agonists have, and are thought to be applicable not only to a pain such as postoperative pain or cancer pain, but also widely to general pains, so that it is thought to be highly useful. Further, since it does not have the cross tolerance, it is expected that the drug is effective to patients having tolerance to an analgesic such as morphine.
As is apparent from the above-mentioned study of the opioid receptors, it is known that antagonists play important roles in the pharmacological studies of receptors, and antagonists at .epsilon.-receptor are expected to be important tools in the pharmacological study of this receptor.